Autoinjector and method of assembling

ABSTRACT

The disclosure further relates to an autoinjector and a method of assembling the autoinjector. A syringe carrier is disclosed comprising a housing adapted to receive a syringe. They syringe includes a needle encapsulated by a removable protective needle sheath. The syringe carrier further includes two or more flexible arms protruding outwards in a relaxed state and adapted to couple with the syringe in a mounted position. In the mounted position, the flexible arms deflect radially inwards due, in part, to an axial force operating on the syringe carrier.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is the national stage entry of InternationalPatent Application No. PCT/EP2016/062462, filed on Jun. 2, 2016, andclaims priority to Application No. EP 15170597.7, filed on Jun. 3, 2015,the disclosures of which are expressly incorporated herein in entiretyby reference thereto.

TECHNICAL FIELD

The disclosure relates to an autoinjector and method of assembling theautoinjector.

BACKGROUND

Administering an injection is a process that presents a number of mentaland physical risks and challenges for users and healthcareprofessionals. Injection devices typically fall into twocategories—manual devices and autoinjectors. In a conventional manualdevice, manual force is required to drive a medicament through a needle.This is typically done by a plunger, which is continuously pressedduring the injection. There are numerous disadvantages associated withthis approach. For example, if the plunger is released prematurely, theinjection will stop and may not deliver an intended dose. Furthermore,the force required to push the plunger may be too high (e.g., if theuser is elderly or a child). Additionally, aligning the injectiondevice, administering the injection, and keeping the injection devicestill during the injection, may require dexterity which some patientsmay not have.

Autoinjector devices aim to make self-injection easier for patients. Aconventional autoinjector may provide the force for administering theinjection by a spring, a trigger button, or other mechanisms used toactivate the injection. Autoinjectors may be single-use or reusabledevices.

SUMMARY

According to aspects of the current disclosure, there is provided asyringe carrier for an autoinjector comprising a housing adapted toreceive a syringe having a needle encapsulated by a removable protectiveneedle sheath, and two or more flexible arms protruding outwards in arelaxed state and adapted to couple with the syringe in a mountedposition, wherein in the mounted position, the flexible arms aredeflected radially inwards due, in part, to an axial force operating onthe syringe carrier.

The flexible arms are deflected radially inwards due to a relativemovement of the syringe carrier with respect to the syringe. Thisrelative movement may be caused by the axial force on the syringecarrier. The inward deflection of the flexible arms is provided by aramp control. For example, the case comprises a ramp at its innersurface.

In an exemplary embodiment, the flexible arms extend distally from acarrier front end. In a further exemplary embodiment, the flexible armsare symmetrically arranged around the carrier front end. The flexiblearms protrude radially outwards in a relaxed state.

In an exemplary embodiment, the flexible arms, in particular a distalend of the flexible arms comprise protrusions inwardly directed onto thesyringe and configured to couple with a distal shoulder of the syringe.Preferably, the syringe is a pre-filled syringe having a needle.Alternatively, a medicament container having a needle may be provided.

According to a further embodiment, an outer diameter of the protrusionsis smaller than an outer diameter of the protective needle sheath and anouter diameter of a shaft of the syringe. The smaller outer diameter ofthe protrusions supports and thus pre-positions the syringe at an axialposition with respect to the syringe carrier and the protective needlesheath in the final mounted position.

In an exemplary embodiment, the housing includes a proximal aperturehaving an outer diameter, in part, smaller than an outer diameter of aproximal syringe flange. When moving the syringe within the syringecarrier, the proximal syringe flange engages and rests onto a carrierrear end of the proximal aperture. Preferably, the proximal aperture hasan elliptical or oval form and thus the outer diameter of the proximalaperture may be smaller as well as larger than the circular outerdiameter of the proximal syringe flange.

According to another aspect of the current disclosure, there is providedan autoinjector comprising at least a syringe carrier and a case adaptedto receive the syringe carrier.

In an exemplary embodiment, the case is adapted to inwardly deflect theflexible arms in the mounted position when the axial force operates ontothe syringe carrier. In an exemplary embodiment, the case comprises atleast one inwardly directed edge, e.g. a ramp, operating onto theflexible arms wherein the inward deflection of the flexible arms in themounted position forces the syringe and the protective needle sheathapart when the axial force operates onto the syringe carrier. The designof the syringe carrier and the case are such that a protective needlesheath, e.g. a rigid or a rubber needle sheath, is automaticallydisplaced to a predetermined position during assembly to providesufficient clearance to support the syringe at the datum.

In an exemplary embodiment, the case comprises at least one inwardlydirected rigid edge, e.g. circumferential-ridged edge or latches, at adistal end in the direction of the protective needle sheath. In anotherembodiment, the edge is formed as a ramp.

In an exemplary embodiment, the syringe carrier comprises holding clampson an axial carrier rear end, e.g. opposite to the direction of theprotective needle sheath for releasable holding of the syringe carrierin the case. The holding clamps are integrally formed with the syringecarrier, e.g. as tongues. In particular, the holding clamps areoutwardly directed. Furthermore, the syringe carrier comprises at leasttwo clamps arranged opposite to each other on a carrier rear end, e.g.on a carrier flange or carrier head.

In an exemplary embodiment, the case comprises at least one innersupport to releasably hold the holding clamps. In particular, the innersupport may be formed as an inner groove or slot or opening.

In an exemplary embodiment, the case comprises a front case and a rearcase.

The front case may be adapted to releasably hold the carrier at its rearend and to fixedly hold the carrier at its front end. Furthermore, thefront case is adapted to enclose the autoinjector and to deflect theflexible arms of the carrier radially inwards in the mounted position.

Furthermore, the rear case is adapted to prevent axial movement of thesyringe relative to the case and to close an axial case end opposite tothe direction of the protective needle sheath.

In an exemplary embodiment, the autoinjector further comprises a needleshroud telescopically coupled to the case and movable between anextended position relative to the case in which the needle is coveredand a retracted position relative to the case in which the needle isexposed, a shroud spring biasing the needle shroud in a distal directionrelative to the case, a plunger slidably disposed in the case, and adrive spring to drive the plunger.

In an exemplary embodiment, the case comprises the front case and therear case which is surrounded by the front case along a longitudinaldirection and adapted to close an open proximal end of the front case.

In an exemplary embodiment, the needle shroud includes an inner shroudboss on which an inner case boss of the case abuts.

In an exemplary embodiment, due to an axial force applied to the rearend of the syringe carrier, the holding clamps are released from thecase so that the syringe carrier together with the assembled syringe maybe moved within the case.

In an exemplary embodiment, the case comprises one or more openings orone or more apertures to allow insertion of at least one assembling toolfor applying a force to release the at least one holding clamp of thesyringe carrier from the case and to move the syringe carrier within thecase.

According to a further aspect of the current disclosure, a method ofassembling an autoinjector is provided and comprises the steps of:providing a case in which a syringe carrier with flexible armsprotruding inwards in a relaxed state is mounted, providing a syringewith a needle encapsulated by a removable protective needle sheath,inserting and pre-positioning the syringe axially into the syringecarrier and inserting a front-assembling tool at a distal end of thecase and a back-assembling tool at a proximal end of the case, finallymounting the syringe into the syringe carrier by releasing the syringecarrier from the case and moving the syringe carrier forwards within thecase until the flexible arms are deflected radially inwards to couplewith the syringe in the mounted position due, in part, to an axial forceoperating on the syringe carrier.

The inward deflection of the flexible arms in the mounted and finalposition displaces the protective needle sheath to allow space tosupport the syringe at its datum. In this mounted position, the flexiblearms of the syringe carrier are held rigidly by the case, e.g. by a rampor edge, and thus safely support the syringe.

The flexible arms radially deflect due, in part, to an axial forceoperating on the syringe carrier, so that the syringe carrier isrelatively moved with respect to the case and, finally, in addition withrespect to the syringe.

In an exemplary embodiment, for inserting the syringe into the syringecarrier, the syringe is moved into an opened carrier rear end axiallyforwards until a syringe flange engages the carrier rear end.

When inserting the syringe into the syringe carrier, for example, aback-assembling tool is pushed axially forward onto the syringe.

In an exemplary embodiment, for releasing the syringe carrier from thecase and moving the syringe carrier forwards within in the case, forexample, a back-assembling tool is pushed axially forward onto thesyringe carrier so that the carrier moves together with the syringe in aforward direction.

For finally mounting and positioning of the syringe within the syringecarrier, when moving the syringe carrier forwards within the case andreaching the mounted position, the syringe carrier with the syringe ismoved forwards until the protective needle sheath of the syringe engagesand comes in contact with the front-assembling tool arranged in the capso that the syringe stops and is fixed. The back-assembling tool keepspushing on the syringe carrier. Due to these further axial forces ontothe syringe carrier, the syringe carrier is further relatively movedwith respect to the syringe until the syringe carrier contacts thefront-assembling tool arranged in the cap. At this point, the flexiblearms engage a case ramp or case edge so that the flexible arms slideover the ramp or edge and are deflected radially inwards when reachingthe final mounted position. In this final mounted position, the flexiblearms engage and displace the protective needle sheath to allow space tosupport the syringe in its final position and at its datum. Further, inthis final mounted position, the case is adapted to restrain and supportthe inward deflection of the flexible arms, forcing the syringe and theprotective needle sheath apart.

According to a further aspect of the current disclosure, a method ofassembling an autoinjector is provided and comprises the steps of:providing a front subassembly comprising a front case with a mountedneedle shroud and an open case rear end in which the syringe carrierwith a carrier front end and a carrier rear end is mounted, providingthe syringe with a needle encapsulated by a removable protective needlesheath, inserting the syringe axially into the case rear end by pushinga syringe flange until the syringe flange engages the carrier rear end,finally mounting the syringe into the carrier by the following steps:releasing the syringe carrier from the case and moving the syringecarrier forwards, so that the syringe carrier together with the syringemoves in a forward direction within the case until the flexible arms aredeflected radially inwards to couple with the syringe in the mountedposition due, in part, to an axial force operating on the syringecarrier.

The case is adapted to restrain the inward deflection of the flexiblearms when the syringe carrier reaches the mounted position such that,due to an axial force acting onto the syringe carrier, the case operatesonto the flexible arms, forcing the syringe and the protective needlesheath apart. The flexible arms engage behind the rear end of theprotective needle sheath. The protective needle sheath and the syringeare spaced apart until the flexible arms are restrained and forcedradially inwards by the case. At this point, the syringe carrier and theprotective needle sheath move as one while the syringe is “left behind”until the flexible arms of the syringe carrier are fully engaged.

The carrier design allows accurate support of the syringe on its datumdespite large variations in syringe and needle shield dimensions and inthe relative positioning of the needle shield and syringe. Inparticular, the syringe carrier, namely the inwardly deflected arms,allows a large syringe datum with a robust support surface with highsafety margin. Furthermore, the final assembling is simplified andallows an axial assembly process.

Further scope of applicability of the present invention will becomeapparent from the detailed description given hereinafter. However, itshould be understood that the detailed description and specificexamples, while indicating exemplary embodiments of the invention, aregiven by way of illustration only, since various changes andmodifications within the spirit and scope of the invention will becomeapparent to those skilled in the art from this detailed description. Thepresent invention will become more fully understood from the detaileddescription given hereinbelow and the accompanying drawings which aregiven by way of illustration only, and thus, are not limitive of thepresent invention.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a simplified longitudinal section of an exemplary embodimentof an autoinjector after assembly,

FIGS. 2A to 2D are schematic perspective partly cut-away views afterassembly (in more detail), an explosion view of an exemplary embodimentof an autoinjector, a perspective view of an exemplary embodiment of aback-assembling tool and a perspective view of an exemplary embodimentof a front-assembling tool,

FIG. 3 is a schematic exploded view of an exemplary embodiment of afront subassembly comprising a front case with a mounted syringe carrierinto which a syringe is to be assembled and of a front-assembling tool,

FIG. 4 is a schematic perspective view of an exemplary embodiment of afront subassembly with a mounted front case into which a syringe and afront-assembling tool are mounted,

FIG. 5 is a schematic enlarged partial view of the rear end of the frontsubassembly,

FIGS. 6A, 6B, 6C are schematic perspective views of an exemplaryembodiment of a front subassembly with a mounted front case into which afront-assembling tool and a back-assembling tool are mounted,

FIGS. 7, 8A, 8B are schematic enlarged partial views of the frontsubassembly with an arranged front-assembling tool,

FIG. 9 is a schematic perspective view of an exemplary embodiment of thefinally positioned front subassembly,

FIG. 10 is a schematic perspective view of an exemplary embodiment ofthe finally positioned front subassembly with removed back-assemblingtool and partially removed front-assembling tool,

FIG. 11 is a schematic enlarged partial view of the finally assembledfront subassembly,

FIG. 12 is a schematic exploded view of a front subassembly and a backsubassembly,

FIG. 13 is a schematic perspective view of the assembled frontsubassembly and back subassembly,

FIG. 14 is schematic enlarged partial view of the distal end of thefinally assembled back subassembly, and

FIG. 15 is a schematic perspective view of an exemplary embodiment of asyringe carrier.

Corresponding parts are marked with the same reference symbols in allfigures.

DETAILED DESCRIPTION

FIG. 1 is a simplified longitudinal section of an exemplary embodimentof an autoinjector 1 after assembly and shows the main assembling parts.FIG. 2A is a schematic perspective partly cut-away view of theautoinjector 1. FIG. 2B shows an explosion view of all components of theautoinjector 1. FIGS. 2A, 2B show the assembled autoinjector 1 in moredetail.

The autoinjector 1 comprises a case 2. The case 2 is designed as amulti-part. In particular, the case 2 comprises a front case 2.1 and arear case 2.2. The rear case 2.2 is surrounded by the front case 2.1along a longitudinal direction and adapted to close an open proximal endof the front case 2.1. The case 2 is adapted to hold a syringe 3.

The syringe 3 may be a pre-filled syringe or a pre-filled medicamentcontainer and has a needle 4 arranged at a distal end. The syringe 3 maybe pre-assembled. Typically, a protective needle sheath 5 may beremovably coupled to the needle 4. The protective needle sheath 5 may bea rubber needle sheath or a rigid needle sheath (which is composed ofrubber and a full or partial plastic shell).

A stopper 6 is arranged for sealing the syringe 3 proximally and fordisplacing a medicament M contained in the syringe 3 through the needle4. In other exemplary embodiments, the syringe may be a cartridge or acontainer which includes the medicament M and engages a removable needle(e.g., by threads, snaps, friction, etc.).

In an exemplary embodiment, a cap 11 may be removably disposed at adistal end of the case 2. The cap 11 may include a grip element 11.2(e.g., a barb, a hook, a narrowed section, etc.) arranged to engage theprotective needle sheath 5, the cap 11 and/or a needle shroud 7telescoped within the case 2. The cap 11 may comprise grip features 11.1for facilitating removal of the cap 11 (e.g., by twisting and/or pullingthe cap 11 relative to the case 2.

Furthermore, the cap 11 comprises a barb 20 grasping the protectiveneedle sheath 5 in a final mounted position of the syringe 3 within thecase 2.

In an exemplary embodiment, a shroud spring 8 (shown in FIG. 2A) isarranged to bias the needle shroud 7 in a distal direction D against thecase 2.

In an exemplary embodiment, a drive spring 9 is arranged within the case2. A plunger 10 serves for forwarding a force of the drive spring 9 tothe stopper 6. In an exemplary embodiment, the plunger 10 is hollow andthe drive spring 9 is arranged within the plunger 10 biasing the plunger10 in the distal direction D against the case 2. In another exemplaryembodiment, the plunger 10 may be solid and the drive spring 9 mayengage a proximal end of the plunger 10. Likewise, the drive spring 9could be wrapped around the outer diameter of the plunger 10 and extendwithin the syringe 3.

In an exemplary embodiment, a plunger release mechanism 12 is arrangedfor preventing release of the plunger 10 prior to retraction of theneedle shroud 7 relative to the case 2, and for releasing the plunger 10once the needle shroud 7 is sufficiently retracted.

In an exemplary embodiment, a shroud lock mechanism 14 is arranged toprevent retraction of the needle shroud 7 relative to the case 2 whenthe cap 11 is in place, thereby avoiding unintentional activation of theautoinjector 1 (e.g., if dropped, during shipping or packaging, etc.).

The shroud lock mechanism 14 may comprise one or more compliant beams11.3 on the cap 11 and a respective number of apertures 7.6 (shown inFIG. 2A) in the needle shroud 7 adapted to receive each of the compliantbeams 11.3. When the cap 11 is attached to the autoinjector 1, thecompliant beams 11.3 abut a radial stop 2.15 on the case 2, whichprevents the compliant beams 11.3 from disengaging the apertures 7.6.

When the cap 11 is attached to the autoinjector 1, axial movement of thecap 11 in the proximal direction P relative the case 2, is limited by arib 11.4 on the cap 11 abutting the case 2. When the cap 11 is pulled inthe distal direction D relative to the case 2, the compliant beams 11.3may abut an edge of the aperture 7.6 and deflect to disengage theaperture 7.6, allowing for removal of the cap 11 and the protectiveneedle sheath 5 attached thereto.

In the shown embodiment, the cap 11 comprises a closable opening 11.5for inserting a front assembling tool 19 (an example is shown in FIG.2D).

In an exemplary embodiment, the compliant beams 11.3 and/or theapertures 7.6 may be ramped to reduce force necessary to disengage thecompliant beams 11.3 from the apertures 7.6.

The autoinjector 1 comprises at least an audible indicator 13 (shown inFIG. 2A) for producing an audible feedback of completion of medicament Mdelivery. The audible indicator 13 is formed, for example, as a bistablespring and is held in the rear case 2.2.

The rear case 2.2 is adapted to prevent axial movement of the syringe 3after assembling, in particular during storage, transportation, andnormal use. In detail, the rear case 2.2 comprises at its front endresilient arms 15. The resilient arms 15 are formed as inwardly directedarms in a relaxed state.

To allow an accurate support of the syringe 3 during and afterassembling, the autoinjector 1 comprises a syringe carrier 16. Thesyringe carrier 16 is adapted to assemble and hold the syringe 3 withinthe case 2 and is further explained in more detail.

In particular, the syringe 3 is a 1.0 ml pre-filled syringe with a rigidprotective needle sheath 5. Usually, the syringe 3 and the protectiveneedle sheath 5 have large variations in dimensions. To allow accuratesupport of the syringe 3 in a mounted position despite these largevariations, the design of the syringe carrier 16 and the front case 2.1are adapted to automatically displace and position the protective needlesheath 5 to a predetermined position during assembly to providesufficient clearance to support the syringe 3 at its datum in themounted position.

Therefore, the syringe carrier 16 comprises flexible arms 16.1 adaptedto mount and position the syringe 3 and hold it in a mounted position.The flexible arms 16.1 protrude outwards in a relaxed state.

The syringe carrier 16 comprises a housing 16.0 adapted to receive thesyringe 3 and at least two flexible arms 16.1 adapted to couple with thesyringe 3 in the mounted position. The housing 16.0 is formed as ahollow cylinder.

he flexible arms 16.1 are distally extended from an axial carrier frontend 16.2 of the housing 16.0. The flexible arms 16.1 protrude outwardsin a relaxed state, e.g. are outwardly formed, e.g. angled. The flexiblearms 16.1 comprise inwardly directed protrusions 16.3 at distal ends ofthe flexible arms 16.1.

To support the final assembly of the syringe 3 into the syringe carrier16, the at least two flexible arms 16.1 are adapted to couple with thesyringe 3 in the mounted position, such that the outwardly protrudedflexible arms 16.1 are deflected radially inwards in the mountedposition due to a relative movement of the syringe carrier 16 withrespect to the syringe 3. This relative movement may be caused by anaxial force operating on the syringe carrier 16, e.g. on a carrier rearend 16.4.

Furthermore, the front case 2.1 is adapted to restrain the inwarddeflection of the flexible arms 16.1 when the syringe 3 is in themounted position, such that an assembled force of the case 2 operatesonto the flexible arms 16.1, forcing the syringe 3 and the protectiveneedle sheath 5 apart, so that the syringe 3 is secured in the mountedposition shown in FIGS. 1 and 2A.

The carrier 16 comprises a carrier rear end 16.4 opposite to the carrierfront end 16.2. At the carrier rear end 16.4, the carrier 16 comprises acarrier flange 16.5 with holding clamps 16.6 for releasable intermittentholding of the carrier 16 relative to the case 2.

The holding clamps 16.6 are integrally formed on the carrier flange 16.5as tongues. Proximal ends of the holding clamps 16.6 are outwardlydirected to engage slots 2.1.1 of the case 2. In an embodiment, thecarrier 16 comprises two holding clamps 16.6 arranged opposite to eachother.

Instead of slots 2.1.1, the front case 2.1 may comprise an inner supportto releasably hold the holding clamps 16.6. In particular, the innersupport may be formed as an inner groove.

Furthermore, the syringe carrier 16 comprises ribs 16.8 on the outersurface of the flexible arms 16.1 to provide a stopping function for therelative movement of the syringe carrier 16 with respect to the syringe3. The ribs 16.8 correspond with cuts or nuts (not shown) within theinner surface of the front case 2.1.

In an exemplary embodiment, the autoinjector 1 may be formed from atleast two subassemblies, e.g., a control or front subassembly 1.1 and adrive or rear subassembly 1.2, to allow for flexibility as to the timeand location of manufacture of the subassemblies 1.1, 1.2 and finalassembly with the syringe 3.

FIGS. 2C and 2D show a perspective view of an exemplary embodiment of aback-assembling tool 18 having rigid arms 18.1 and of a front-assemblingtool 19 having rigid arms 19.1.

FIG. 3 is a perspective exploded view of an exemplary embodiment of afront subassembly 1.1 of an autoinjector 1.

In an exemplary embodiment, the front subassembly 1.1 comprises at leastthe front case 2.1, the needle shroud 7 and the syringe carrier 16, inwhich the syringe 3 is assembled.

The needle shroud 7 and the syringe carrier 16 are mounted into thefront case 2.1. In particular, the syringe carrier 16 is stable due toclamp connection of the holding clamps 16.6 within slots 2.1.1 of thefront case 2.1 at its rear end.

For assembling the syringe 3 into the syringe carrier 16 and thus intothe front case 2.1, the case 2 comprises one or more apertures to allowinsertion of the syringe 3 and insertion of the front-assembling tool19.

As shown in FIG. 3, the case 2, in particular the front case 2.1, isprovided in which the syringe carrier 16 is pre-assembled and mounted.The syringe 3 with the needle 4 encapsulated by the removable protectiveneedle sheath 5 is inserted and pre-positioned axially into the syringecarrier 16 as described in more detail below.

To assemble the front subassembly 1.1, the syringe carrier 16 is axiallyinserted into the front case 2.1 from a proximal end P, until holdingclamps 16.6 of the syringe carrier 16 engage retaining slots 2.1.1 inthe front case 2.1, so that the syringe carrier 16 is fixed and stablein the front case 2.1.

Additionally, the shroud spring 8 is inserted into the needle shroud 7(shown in FIG. 1, not shown in FIG. 4) and the needle shroud 7 with theshroud spring 8 is inserted into a distal end 2.1.2 of the front case2.1. The cap 11 together with the barb 11.2 is arranged over the distalend of the needle shroud 7.

After the syringe carrier 16 is fixed in the front case 2.1, the syringe3 may be inserted into the front subassembly 1.1, namely into thesyringe carrier 16 from its carrier rear end 16.4. In particular, thesyringe 3 is dropped into the opened carrier rear end 16.4 axiallyforwards until the syringe flange 3.1 engages the carrier rear end 16.4as it is shown in FIGS. 4 and 5. In particular, the syringe flange 3.1engages a proximal shoulder 16.5.1 of the carrier flange 16.5.Alternatively, the syringe flange 3.1 engages a distal shoulder of thecarrier flange 16.5.

When inserting the syringe 3 into the syringe carrier 16, thefront-assembling tool 19 is inserted into the front case 2.1. Inparticular, the front-assembling tool 19 is pushed into the cap 11 andonto the protective needle sheath 5 axially forwards.

When the syringe 3 is inserted into the syringe carrier 16, the flexiblearms 16.1 protrude outwards and engage a shaft of the syringe 3 (shownin FIG. 4).

FIG. 4 shows in detail the front subassembly 1.1 with the mountedsyringe carrier 16 together with the mounted syringe 3 in anintermediate assembling position.

As the protective needle sheath 5 is usually larger than the syringediameter, the syringe 3 cannot be assembled into the front case 2.1through the needle shroud 7. To overcome this problem, the syringecarrier 16 is provided. Hence the housing 16.0 of the syringe carrier 16comprises an inner diameter larger than the outer diameter of a shaft ofthe syringe 3. Furthermore, the housing 16.0 includes a proximalaperture having an outer diameter, in part, smaller than an outerdiameter of the proximal syringe flange 3.1.

In this corresponding intermediate assembling position of the frontsubassembly 1.1 with the assembled syringe carrier 16 and the syringe 3,the holding clamps 16.6 are held in the slots 2.1.1 and the flexiblearms 16.1 of the syringe carrier 16 outwardly deflect and sit on thebarrel or shaft of the syringe 3.

As it is shown in FIGS. 6A to 6C, afterwards, for final positioning ofthe syringe 3 within the syringe carrier 16, an axial force according toarrow F1 is then applied to the syringe carrier 16 so that the holdingclamps 16.6 are released from the slots 2.1.1 and the syringe carrier 16together with the syringe 3 is moved within the case 2 into the distaldirection D.

The axial force F1 applied to the syringe carrier 16 is smaller than aholding force, e.g. friction force, between the syringe carrier 16 andthe syringe 3, e.g. between their contacting surfaces.

Furthermore, the axial force F1 is greater than the retention force ofthe holding clamps 16.6 on the front case 2.1.

As it is shown in FIGS. 6A and 6B, for example, the back-assembling tool18 is inserted into the front case 2.1 until it contacts the carrierrear end 16.4. Afterwards, the back-assembling tool 18 is pushed ontothe syringe carrier 16 axially forwards so that the syringe carrier 16is released from the case 2 and moves together with the syringe 3 in aforward direction. As best seen in FIG. 6B, the arms 18.1 of theback-assembling tool 18 are attached to the syringe carrier 16. Thecarrier rear end 16.4 comprises an elliptical or oval form and has anouter diameter, in part, larger than the outer diameter of the syringeflange 3.1.

Due to the axial force according to the arrow F1 acting on the syringecarrier 16, the holding clamps 16.6 are released from the slots 2.1.1 sothat the carrier 16 together with the syringe 3 is moved forwardly. Thesyringe 3 follows this downward or forward movement.

When acting an axial force F1 on the syringe carrier 16 the syringecarrier 16 with the syringe 3 is moved forwards within the case 2 untilthe syringe 3, in particular the protective needle sheath 5, engages andcomes in contact with the inserted front-assembling tool 19, so that thesyringe 3 is stopped and fixed, as shown in FIGS. 6C and 7.

FIG. 7 shows the engagement of the distal end of the protective needlesheath 5 with a stamp 19.2 of the front-assembling tool 19 so that thesyringe 3 is stopped and fixed in the front case 2.1.

FIG. 8A shows the further assembling step, wherein the back-assemblingtool 18 is further pushed onto the syringe carrier 16 so that thesyringe carrier 16 is further moved with respect to the syringe 3 withinthe case 2, until the syringe carrier 16 also comes in contact with thefront-assembling tool 19. In particular, the arms 19.1 are inserted intothe distal end of the syringe carrier 16 until the arms 19.1 engageinner edges 16.9 of the syringe carrier 16, as shown in FIG. 7. Due tofurther axial force F1 to the syringe carrier 16, the front-assemblingtool 19 is also moved forwards and extends partially out of the cap 11,as best seen in FIG. 9.

At this point, the flexible arms 16.1 are ready to engage the front case2.1, in particular the edge 2.1.3. The edge 2.1.3 is formed as a ramp,e.g. a guiding ramp to control the inward deflection of the flexiblearms 16.1. The flexible arms 16.1 enter the ramps and are deflectedinwards to couple with the distal end of the syringe 3 in the finalmounted position. The movement of the syringe carrier 16 is stopped asthe ribs 16.8 on the back of the flexible arms 16.1 engage a cut end ornut end arranged in the front case 2.1.

In this final mounted position, the flexible arms 16.1 engage anddisplace the protective needle sheath 5 to allow space to support thesyringe 3 in the final position and at the datum. Furthermore, in thisfinal mounted position, the case 2, in particular the ramp, is adaptedto restrain and support the inward deflection of the flexible arms 16.1,forcing the syringe 3 and the protective needle sheath 5 apart.

During assembling and providing the axial force F1 onto the syringecarrier 16, the flexible arms 16.1 are inwardly deflected and restrainedin the mounted position by the edge 2.1.3 according to arrow F2 so thatthe protective needle sheath 5 is displaced according to arrows F3 toallow space between the syringe 3 and the protective needle sheath 5 andto support and position the syringe 3 in the final mounted position.Alternatively, the radially inwards deflected flexible arms 16.1 arepositioned a distance from the proximal end of the protective needlesheath 5, e.g. in a distance of minus 0.3 mm.

As shown in FIG. 8B, in the final mounted position, the flexible arms16.1 of the syringe carrier 16 are rigidly held and stable by the edge2.1.3 of the front case 2.1 to safely support and position the syringe3.

FIG. 9 shows the syringe carrier 16 and the syringe 3 in the finalmounted position. The front-assembling tool 19 is partially pushed outof the cap 11.

FIG. 10 shows the further assembling step wherein the back-assemblingtool 18 is removed. The length of the syringe carrier 16 may be smallerthan the length of the syringe 3 to be assembled. The front-assemblingtool 19 is further removed from the cap 11 enabling the protectiveneedle sheath 5, as well as the syringe 3 and the syringe carrier 16,due to the engagement of the inwardly deflected arms 16.1 onto thedistal end of the syringe 3, to move and fall into the cap 11. Due tothe inserted front-assembling tool 19, cap arms 11.6 are deflectedoutwards as shown in FIG. 11 to support the further movement of thesyringe 3 and the syringe carrier 16 into the cap 11.

Due to this further movement of the syringe 3 into the distal directionD, the distal end (datum) of the syringe 3 hits the flexible arms 16.1of the syringe carrier 16 in the final mounting position.

FIGS. 12 to 14 show the last assembling step, wherein the frontassembling tool 19 is completely removed, allowing the cap arms 11.6 toclose up and engage on the protective needle sheath 5.

The rear case 2.2 is ready to insert into the proximal end of the frontcase 2.1. The resilient arms 15 ensure that the syringe 3 cannot movebackwards into the proximal direction P.

here is a risk that, during the last assembling step, the forces fromthe removing of the front-assembling tool 19, including gravitationalforce, do not enable the protective needle sheath 5 to fall into the cap11. Consequently, the syringe 3 does not come into distal contact withthe protrusions 16.3 of the flexible arms 16.1 of the syringe carrier16. In order to solve this issue, the rear case 2.2 could be insertedand pushed on the syringe 3 until the syringe datum contacts theprotrusions 16.3

In summary, FIG. 1 shows a longitudinal section of the autoinjector 1after final assembly, wherein the rear subassembly 1.2 (also calleddrive subassembly) is mounted onto the front subassembly 1.1.

In an exemplary embodiment, the rear subassembly 1.2 comprises theplunger 10, the drive spring 9 and the rear case 2.2. Those of skill inthe art will understand that if the viscosity or volume, for example, ofthe medicament M in the syringe 3 is changed, only parts of the rearsubassembly 1.2 may need to be changed. To assemble the rear subassembly1.2, the drive spring 9 is inserted into the plunger 10 and the plunger10 is inserted in the rear case 2.2 in the proximal direction P, therebycompressing the drive spring 9. Once the plunger 10 and the drive spring9 reach a compressed position, it is rotated by an angle, e.g.approximately 30° relative to the rear case 2.2, to engage the plunger10 to the rear case 2.2. In an exemplary embodiment, the rear case 2.2may have a cam surface to engage the plunger 10 to induce this rotationprior to the plunger 10 and the drive spring 9 reaching the compressedposition.

In an exemplary embodiment, after the final assembly of the rearsubassembly 1.2 to the front subassembly 1.1, the autoinjector 1 may bekept in temperature controlled environment (e.g., cold chain storage)to, for example, reduce creep in highly stressed components, e.g. underload from the drive spring 9.

In an exemplary embodiment, a force required to press the needle shroud7 may be approximately 2 N to 12 N. Likewise, the mechanism may workwith a higher force.

In an exemplary embodiment, the syringe 3 used in the autoinjector 1 maybe a syringe capable of containing approximately 1 mL of the medicamentM. In another exemplary embodiment, the syringe 3 used in theautoinjector 1 may be a syringe capable of containing approximately 2 mLof the medicament M.

The autoinjector 1 according to the present disclosure may have anincreased shelf-life compared to conventional autoinjectors, because,for example, only the plunger 10 is subjected to the relatively highforce of the drive spring 9.

The autoinjector 1 according to the present disclosure may be used as aplatform as the drive spring 9 can be changed to alter a force appliedto the plunger 10, e.g. for delivering medicaments with differentviscosities drugs or reconstituted medicaments, or changing a timerequired to inject a dose of the medicament.

The cap 11 is suitable for being applied with any kind of injectiondevice or autoinjector. The terms “drug” or “medicament” are used hereinto describe one or more pharmaceutically active compounds. As describedbelow, a drug or medicament can include at least one small or largemolecule, or combinations thereof, in various types of formulations, forthe treatment of one or more diseases. Exemplary pharmaceutically activecompounds may include small molecules; polypeptides, peptides andproteins (e.g., hormones, growth factors, antibodies, antibodyfragments, and enzymes); carbohydrates and polysaccharides; and nucleicacids, double or single stranded DNA (including naked and cDNA), RNA,antisense nucleic acids such as antisense DNA and RNA, small interferingRNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids maybe incorporated into molecular delivery systems such as vectors,plasmids, or liposomes. Mixtures of one or more of these drugs are alsocontemplated.

The term “drug delivery device” shall encompass any type of device orsystem configured to dispense a drug into a human or animal body.Without limitation, a drug delivery device may be an injection device(e.g., syringe, pen injector, auto injector, large-volume device, pump,perfusion system, or other device configured for intraocular,subcutaneous, intramuscular, or intravascular delivery), skin patch(e.g., osmotic, chemical, micro-needle), inhaler (e.g., nasal orpulmonary), implantable (e.g., coated stent, capsule), or feedingsystems for the gastro-intestinal tract. The presently described drugsmay be particularly useful with injection devices that include a needle,e.g., a small gauge needle.

The drug or medicament may be contained in a primary package or “drugcontainer” adapted for use with a drug delivery device. The drugcontainer may be, e.g., a cartridge, syringe, reservoir, or other vesselconfigured to provide a suitable chamber for storage (e.g., short- orlong-term storage) of one or more pharmaceutically active compounds. Forexample, in some instances, the chamber may be designed to store a drugfor at least one day (e.g., 1 to at least 30 days). In some instances,the chamber may be designed to store a drug for about 1 month to about 2years. Storage may occur at room temperature (e.g., about 20° C.), orrefrigerated temperatures (e.g., from about −4° C. to about 4° C.). Insome instances, the drug container may be or may include a dual-chambercartridge configured to store two or more components of a drugformulation (e.g., a drug and a diluent, or two different types ofdrugs) separately, one in each chamber. In such instances, the twochambers of the dual-chamber cartridge may be configured to allow mixingbetween the two or more components of the drug or medicament prior toand/or during dispensing into the human or animal body. For example, thetwo chambers may be configured such that they are in fluid communicationwith each other (e.g., by way of a conduit between the two chambers) andallow mixing of the two components when desired by a user prior todispensing. Alternatively or in addition, the two chambers may beconfigured to allow mixing as the components are being dispensed intothe human or animal body.

The drug delivery devices and drugs described herein can be used for thetreatment and/or prophylaxis of many different types of disorders.Exemplary disorders include, e.g., diabetes mellitus or complicationsassociated with diabetes mellitus such as diabetic retinopathy,thromboembolism disorders such as deep vein or pulmonarythromboembolism. Further exemplary disorders are acute coronary syndrome(ACS), angina, myocardial infarction, cancer, macular degeneration,inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis.

Exemplary drugs for the treatment and/or prophylaxis of diabetesmellitus or complications associated with diabetes mellitus include aninsulin, e.g., human insulin, or a human insulin analogue or derivative,a glucagon-like peptide (GLP-1), GLP-1 analogues or GLP-1 receptoragonists, or an analogue or derivative thereof, a dipeptidyl peptidase-4(DPP4) inhibitor, or a pharmaceutically acceptable salt or solvatethereof, or any mixture thereof. As used herein, the term “derivative”refers to any substance which is sufficiently structurally similar tothe original substance so as to have substantially similar functionalityor activity (e.g., therapeutic effectiveness).

Exemplary insulin analogues are Gly(A21), Arg(B31), Arg(B32) humaninsulin (insulin glargine); Lys(B3), Glu(B29) human insulin; Lys(B28),Pro(B29) human insulin; Asp(B28) human insulin; human insulin, whereinproline in position B28 is replaced by Asp, Lys, Leu, Val or Ala andwherein in position B29 Lys may be replaced by Pro; Ala(B26) humaninsulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30)human insulin.

Exemplary insulin derivatives are, for example, B29-N-myristoyl-des(B30)human insulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoylhuman insulin; B29-N-palmitoyl human insulin; B28-N-myristoylLysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N-(N-palmitoyl-gamma-glutamyl)-des(B30) humaninsulin; B29-N-(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(ω-carboxyheptadecanoyl) human insulin. Exemplary GLP-1, GLP-1analogues and GLP-1 receptor agonists are, for example:Lixisenatide/AVE0010/ZP10/Lyxumia,Exenatide/Exendin-4/Byetta/Bydureon/ITCA 650/AC-2993 (a 39 amino acidpeptide which is produced by the salivary glands of the Gila monster),Liraglutide/Victoza, Semaglutide, Taspoglutide, Syncria/Albiglutide,Dulaglutide, rExendin-4, CJC-1134-PC, PB-1023, TTP-054,Langlenatide/HM-11260C, CM-3, GLP-1 Eligen, ORMD-0901, NN-9924, NN-9926,NN-9927, Nodexen, Viador-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697,DA-3091, MAR-701, MAR709, ZP-2929, ZP-3022, TT-401, BHM-034. MOD-6030,CAM-2036, DA-15864, ARI-2651, ARI-2255, Exenatide-XTEN andGlucagon-Xten.

An exemplary oligonucleotide is, for example: mipomersen/Kynamro, acholesterol-reducing antisense therapeutic for the treatment of familialhypercholesterolemia.

Exemplary DPP4 inhibitors are Vildagliptin, Sitagliptin, Denagliptin,Saxagliptin, Berberine.

Exemplary hormones include hypophysis hormones or hypothalamus hormonesor regulatory active peptides and their antagonists, such asGonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin),Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin,Triptorelin, Leuprorelin, Buserelin, Nafarelin, and Goserelin.

Exemplary polysaccharides include a glucosaminoglycane, a hyaluronicacid, a heparin, a low molecular weight heparin or an ultra-lowmolecular weight heparin or a derivative thereof, or a sulphatedpolysaccharide, e.g. a poly-sulphated form of the above-mentionedpolysaccharides, and/or a pharmaceutically acceptable salt thereof Anexample of a pharmaceutically acceptable salt of a poly-sulphated lowmolecular weight heparin is enoxaparin sodium. An example of ahyaluronic acid derivative is Hylan G-F 20/Synvisc, a sodiumhyaluronate.

The term “antibody”, as used herein, refers to an immunoglobulinmolecule or an antigen-binding portion thereof. Examples ofantigen-binding portions of immunoglobulin molecules include F(ab) andF(ab′)₂ fragments, which retain the ability to bind antigen. Theantibody can be polyclonal, monoclonal, recombinant, chimeric,de-immunized or humanized, fully human, non-human, (e.g., murine), orsingle chain antibody. In some embodiments, the antibody has effectorfunction and can fix complement. In some embodiments, the antibody hasreduced or no ability to bind an Fc receptor. For example, the antibodycan be an isotype or subtype, an antibody fragment or mutant, which doesnot support binding to an Fc receptor, e.g., it has a mutagenized ordeleted Fc receptor binding region.

The terms “fragment” or “antibody fragment” refer to a polypeptidederived from an antibody polypeptide molecule (e.g., an antibody heavyand/or light chain polypeptide) that does not comprise a full-lengthantibody polypeptide, but that still comprises at least a portion of afull-length antibody polypeptide that is capable of binding to anantigen. Antibody fragments can comprise a cleaved portion of a fulllength antibody polypeptide, although the term is not limited to suchcleaved fragments. Antibody fragments that are useful in the presentdisclosure include, for example, Fab fragments, F(ab′)2 fragments, scFv(single-chain Fv) fragments, linear antibodies, monospecific ormultispecific antibody fragments such as bispecific, trispecific, andmultispecific antibodies (e.g., diabodies, triabodies, tetrabodies),minibodies, chelating recombinant antibodies, tribodies or bibodies,intrabodies, nanobodies, small modular immunopharmaceuticals (SMIP),binding-domain immunoglobulin fusion proteins, camelized antibodies, andVHH containing antibodies. Additional examples of antigen-bindingantibody fragments are known in the art.

The terms “Complementarity-determining region” or “CDR” refer to shortpolypeptide sequences within the variable region of both heavy and lightchain polypeptides that are primarily responsible for mediating specificantigen recognition. The term “framework region” refers to amino acidsequences within the variable region of both heavy and light chainpolypeptides that are not CDR sequences, and are primarily responsiblefor maintaining correct positioning of the CDR sequences to permitantigen binding. Although the framework regions themselves typically donot directly participate in antigen binding, as is known in the art,certain residues within the framework regions of certain antibodies candirectly participate in antigen binding or can affect the ability of oneor more amino acids in CDRs to interact with antigen.

Exemplary antibodies are anti PCSK-9 mAb (e.g., Alirocumab), anti IL-6mAb (e.g., Sarilumab), and anti IL-4 mAb (e.g., Dupilumab).

The compounds described herein may be used in pharmaceuticalformulations comprising (a) the compound(s) or pharmaceuticallyacceptable salts thereof, and (b) a pharmaceutically acceptable carrier.The compounds may also be used in pharmaceutical formulations thatinclude one or more other active pharmaceutical ingredients or inpharmaceutical formulations in which the present compound or apharmaceutically acceptable salt thereof is the only active ingredient.Accordingly, the pharmaceutical formulations of the present inventionencompass any formulation made by admixing a compound described hereinand a pharmaceutically acceptable carrier.

Pharmaceutically acceptable salts of any drug described herein are alsocontemplated for use in drug delivery devices. Pharmaceuticallyacceptable salts are for example acid addition salts and basic salts.Acid addition salts are e.g. HCl or HBr salts. Basic salts are e.g.salts having a cation selected from an alkali or alkaline earth metal,e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), whereinR1 to R4 independently of each other mean: hydrogen, an optionallysubstituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenylgroup, an optionally substituted C6-C10-aryl group, or an optionallysubstituted C6-C10-heteroaryl group. Further examples ofpharmaceutically acceptable salts are known to those of skill in thearts.

Pharmaceutically acceptable solvates are for example hydrates oralkanolates such as methanolates or ethanolates.

Those of skill in the art will understand that modifications (additionsand/or removals) of various components of the substances, formulations,apparatuses, methods, systems and embodiments described herein may bemade without departing from the full scope and spirit of the presentinvention, which encompass such modifications and any and allequivalents thereof.

REFERENCE LIST

-   1 autoinjector-   1.1 front subassembly-   1.2 rear subassembly-   2 case-   2.1 front case-   2.1.1 slots-   2.1.2 distal end of front case-   2.1.3 edge-   2.2 rear case-   2.15 radial stop-   3 syringe-   3.1 syringe flange-   4 needle-   5 protective needle sheath-   6 stopper-   7 needle shroud-   8 shroud spring-   9 drive spring-   10 plunger-   11 cap-   11.1 grip features-   11.2 grip element-   11.3 compliant beams-   11.4 rib-   11.5 opening-   11.6 cap arm-   12 plunger release mechanism-   13 audible indicator-   14 shroud lock mechanism-   15 resilient arms-   16 syringe carrier-   16.0 housing-   16.1 flexible arms-   16.2 carrier front end-   16.3 protrusions-   16.4 carrier rear end-   16.5 carrier flange-   16.5.1 proximal shoulder-   16.6 holding clamps-   16.7 support element-   16.8 rib-   17 viewing window-   18 back-assembling tool-   18.1 arms-   19 front-assembling tool-   19.1 arms-   19.2 stamp-   F1 to F3 arrow-   D distal end-   M medicament-   P proximal end

1-15. (canceled)
 16. An autoinjector comprising: a syringe carriercomprising a housing adapted to receive a syringe having a needleencapsulated by a removable protective needle sheath, a case adapted toreceive the syringe carrier, and two or more flexible arms protrudingoutwards in a relaxed state and adapted to couple with the syringe in amounted position, wherein in the mounted position the flexible arms aredeflected radially inwards due, in part, to an axial force operating onthe syringe carrier.
 17. The autoinjector according to claim 16, whereinthe inward deflection of the flexible arms is provided by a rampcontrol.
 18. The autoinjector according to claim 16, wherein theflexible arms extend distally from a front end of the syringe carrier.19. The autoinjector according to claim 16, wherein the flexible armscomprise protrusions inwardly directed and configured to couple with adistal shoulder of the syringe.
 20. The autoinjector according to claim19, wherein an inner diameter of the protrusions is smaller than anouter diameter of the protective needle sheath and an outer diameter ofa shaft of the syringe.
 21. The autoinjector according claim 16, whereinthe housing includes a proximal aperture having an outer diameter, inpart, smaller than an outer diameter of a proximal syringe flange. 22.The autoinjector according to claim 16, wherein the case is adapted toinwardly deflect the flexible arms in the mounted position when theaxial force operates onto the syringe carrier.
 23. The autoinjectoraccording to claim 16, wherein the case comprises at least one inwardlydirected edge operating onto the flexible arms, forcing the syringe andthe protective needle sheath apart when the axial force operates ontothe syringe carrier.
 24. The autoinjector according to claim 23, whereinthe case edge is formed as a ramp.
 25. The autoinjector according toclaim 16, wherein the case comprises one or more apertures to allowinsertion of at least one assembling tool for applying a force torelease at least one holding clamp of the syringe carrier from the caseand to move the syringe carrier within the case.
 26. A method ofassembling an autoinjector, the method comprising: inserting andpre-positioning a syringe axially into a syringe carrier, the syringecomprising a needle encapsulated by a removable protective needlesheath, and the syringe carrier comprising a housing adapted to receivethe syringe and inserting a front-assembling tool at a distal end of acase that is adapted to receive the syringe carrier, and inserting aback-assembling tool at a proximal end of the case, and mounting thesyringe into the syringe carrier by releasing the syringe carrier fromthe case and moving the syringe carrier forwards within the case untilflexible arms that protrude outwards in a relaxed state are deflectedradially inwards to couple with the syringe in a mounted position due,in part, to an axial force operating on the syringe carrier.
 27. Themethod of assembling an autoinjector according to claim 26, wherein, forinserting the syringe into the syringe carrier, the syringe is movedinto an opened carrier rear end axially forwards until a syringe flangeengages the carrier rear end.
 28. The method of assembling according toclaim 27, wherein, when inserting the syringe into the syringe carrier,the back-assembling tool is pushed onto the syringe axially forwards.29. The method of assembling an autoinjector according claim 26,wherein, for releasing the syringe carrier from the case and moving thesyringe carrier forwards within in the case, the back-assembling tool ispushed onto the syringe carrier axially forwards so that the syringecarrier moves together with the syringe in a forward direction.
 30. Themethod of assembling an autoinjector according to claim 29, wherein,when moving the syringe carrier forwards within the case and reachingthe mounted position, the case is adapted to inwardly deflect theflexible arms, forcing the syringe and the protective needle sheathapart.